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二甲双胍和益生菌在改善乙醇诱导的肝损伤模型中氧化应激和炎症反应中的相互作用。

Metformin and Probiotics Interplay in Amelioration of Ethanol-Induced Oxidative Stress and Inflammatory Response in an and Model of Hepatic Injury.

机构信息

Department of Biological Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa, 388421 Anand, Gujarat, India.

出版信息

Mediators Inflamm. 2021 Apr 15;2021:6636152. doi: 10.1155/2021/6636152. eCollection 2021.

Abstract

Alcohol-induced liver injury implicates inflammation and oxidative stress as important mediators. Despite rigorous research, there is still no Food and Drug Administration (FDA) approved therapies for any stage of alcoholic liver disease (ALD). Interestingly, metformin (Met) and several probiotic strains possess the potential of inhibiting alcoholic liver injury. Therefore, we investigated the effectiveness of combination therapy using a mixture of eight strains of lactic acid-producing bacteria, commercialized as Visbiome® (V) and Met in preventing the ethanol-induced hepatic injury using and models. Human HepG2 cells and male Wistar rats were exposed to ethanol and simultaneously treated with probiotic V or Met alone as well as in combination. Endoplasmic reticulum (ER) stress markers, inflammatory markers, lipid metabolism, reactive oxygen species (ROS) production, and oxidative stress were evaluated, using qRT-PCR, Oil red O staining, fluorimetry, and HPLC. , probiotic V and Met in combination prevented ethanol-induced cellular injury, ER stress, oxidative stress, and regulated lipid metabolism as well as inflammatory response in HepG2 cells. Probiotic V and Met also promoted macrophage polarization towards the M2 phenotype in ethanol-exposed RAW 264.7 macrophage cells. , combined administration of probiotic V and Met ameliorated the histopathological changes, inflammatory response, hepatic markers (liver enzymes), and lipid metabolism induced by ethanol. It also improved the antioxidant markers (HO-1 and Nrf-2), as seen by their protein levels in both HepG2 cells as well as liver tissue using ELISA. Hence, probiotic V may act, in addition to the Met, as an effective preventive treatment against ethanol-induced hepatic injury.

摘要

酒精性肝损伤涉及炎症和氧化应激作为重要的介质。尽管进行了严格的研究,但对于任何阶段的酒精性肝病(ALD),仍然没有获得美国食品和药物管理局(FDA)批准的治疗方法。有趣的是,二甲双胍(Met)和几种益生菌菌株具有抑制酒精性肝损伤的潜力。因此,我们使用混合了八种产乳酸细菌的混合物(商业化的 Visbiome®(V)和 Met),研究了联合治疗对预防乙醇诱导的肝损伤的有效性,使用 和 模型。将人 HepG2 细胞和雄性 Wistar 大鼠暴露于乙醇中,并同时单独用益生菌 V 或 Met 以及联合治疗进行处理。使用 qRT-PCR、油红 O 染色、荧光计和 HPLC 评估内质网(ER)应激标志物、炎症标志物、脂质代谢、活性氧(ROS)产生和氧化应激。结果表明,益生菌 V 和 Met 联合预防了 HepG2 细胞中乙醇诱导的细胞损伤、ER 应激、氧化应激以及调节脂质代谢和炎症反应。益生菌 V 和 Met 还促进了乙醇暴露的 RAW 264.7 巨噬细胞中巨噬细胞向 M2 表型的极化。体内研究结果表明,联合给予益生菌 V 和 Met 可改善乙醇引起的肝组织病理变化、炎症反应、肝标志物(肝酶)和脂质代谢。它还改善了抗氧化标志物(HO-1 和 Nrf-2),这在 HepG2 细胞和肝组织中均通过 ELISA 观察到其蛋白水平。因此,益生菌 V 除了 Met 之外,还可以作为一种有效的预防乙醇诱导的肝损伤的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/647c/8064785/99878f0905a3/MI2021-6636152.001.jpg

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